Project Summary/Abstract Functional near-infrared spectroscopy (fNIRS) is a well-established neuroimaging method which enables neuroscientists to study brain activity by non-invasively monitoring hemodynamic changes in the cerebral cortex. In the last decade, the use of fNIRS has increased significantly with the formation of a society, with an exponential growth of users and publications, and with an increasing number of available commercial instruments. Despite these successes, the impact of fNIRS as a neuroimaging method could be greatly enhanced by addressing several technological limitations. In line with the BRAIN Initiative RFA EB-17-004 ?Development of Next Generation Human Brain Imaging Tools and Technologies? we propose to develop completely novel methodology to measure human brain function, time-gated functional diffuse correlation spectroscopy (fDCS), which will dramatically improve upon the capabilities of fNIRS. DCS, a cutting-edge optical modality, quantifies relative blood flow changes (rCBF) by measuring the light intensity temporal fluctuations generated by the dynamic scattering of light by moving red blood cells. A few years ago, we demonstrated the ability to operate DCS in the time-domain, and supported by the parent early stage RFA EB-17-001, developed the first portable time-gated fDCS system. With this device we can discriminate late from early arriving photon, obtaining blood flow measures only from photons which have travelled deeper into the tissue, further increasing sensitivity to brain. Our established team, which includes investigators from Massachusetts General Hospital, Massachusetts Institute of Technology Lincoln Laboratory, and Boston University, is now ready to make a leap forward in this technology with the goal to offer an imaging system that covers the whole adult head while producing high resolution images of functional blood flow changes with 2-3x improvements in contrast to noise ratio, brain sensitivity and resistance to extracerebral physiology cross-talk. This goal will be achieved by: i) using a longer wavelength, specifically 1064 nm, where a multitude of factors combine to offer a 10x increase in light throughput, as well as lower scattering for increased penetration depth and spatial resolution; ii) developing new laser and detectors with optimal specifications for time-gated fDCS, overcoming limitations of current commercially available components; iii) scaling-up the new components to build a multichannel system and an high density fiber optic cap with 96 sources and 192 detectors distributed in a hexagonal pattern with an ~13mm separation, for a total of 576 channels, to produce high resolution images of functional blood flow changes. The novel time- gated fDCS system will be characterized in tissue-like phantoms, and validated in healthy volunteers during standard functional tasks, against continuous-wave NIRS, DCS and fMRI. The development of this technology will provide an unprecedented tool to characterize human brain function.